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L-Menthol-Loadable Electrospun Fibers of PMVEMA Anhydride for Topical Administration
Amalia Mira1, Marta Rubio-Camacho1, David Alarcón1
1Institute of Research Development and Innovation in Biotechnology of Elche (IDiBE), Miguel Hernández University (UMH), 03202 Elche, Spain.
Abstract:
Poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) of 119 and 139 molecular weights (P119 and P139, respectively) were electrospun to evaluate the resulting fibers as a topical delivery vehicle for (L-)menthol. Thus, electrospinning parameters were optimized for the production of uniform bead-free fibers from 12% w/w PMVEMA (±2.3% w/w menthol) solutions, and their morphology and size were characterized by field emission scanning electron microscopy (FESEM). The fibers of P119 (F119s) and P139 (F139s) showed average diameter sizes of approximately 534 and 664 nm, respectively, when unloaded, and 837 and 1369 nm when loaded with menthol. The morphology of all types of fibers was cylindrical except for F139s, which mostly displayed a double-ribbon-like shape. Gas chromatography-mass spectrometry (GC-MS) analysis determined that not only was the menthol encapsulation efficiency higher in F139s (92% versus 68% in F119s) but also that its stability over time was higher, given that in contrast with F119s, no significant losses in encapsulated menthol were detected in the F139s after 10 days post-production. Finally, in vitro biological assays showed no significant induction of cytotoxicity for any of the experimental fibers or in the full functionality of the encapsulated menthol, as it achieved equivalent free-menthol levels of activation of its specific receptor, the (human) transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8).
Insights
Poly(methyl vinyl ether-alt-maleic anhydride) fibers effectively deliver menthol topically. Higher molecular weight fibers show superior menthol encapsulation and stability, with no observed cytotoxicity.
Area of Science:
- Materials Science
- Polymer Chemistry
- Drug Delivery
Background:
- Poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) is explored for topical drug delivery.
- Menthol is a common active pharmaceutical ingredient for topical applications.
Purpose of the Study:
- To evaluate electrospun PMVEMA fibers as a topical delivery vehicle for (L-)menthol.
- To optimize electrospinning parameters for uniform, bead-free PMVEMA fibers.
- To characterize the morphology, menthol encapsulation efficiency, and stability within the fibers.
Main Methods:
- Electrospinning of PMVEMA with varying molecular weights (P119, P139) and menthol loading.
- Field emission scanning electron microscopy (FESEM) for fiber morphology and size analysis.
- Gas chromatography-mass spectrometry (GC-MS) for encapsulation efficiency and stability assessment.
- In vitro cytotoxicity assays and TRPM8 receptor activation studies.
Main Results:
- Uniform, bead-free PMVEMA fibers were produced with optimized electrospinning parameters.
- Fibers loaded with menthol showed increased diameters (F119: 837 nm, F139: 1369 nm).
- Higher molecular weight PMVEMA fibers (F139) exhibited superior menthol encapsulation (92%) and stability over 10 days compared to lower molecular weight fibers (F119: 68%).
- No significant cytotoxicity was observed for any fiber type.
- Encapsulated menthol demonstrated equivalent activation of the TRPM8 receptor as free menthol.
Conclusions:
- Electrospun PMVEMA fibers are promising topical delivery systems for menthol.
- Higher molecular weight PMVEMA enhances menthol encapsulation and long-term stability.
- The developed fibers are safe and maintain the biological activity of menthol.
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